کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
11020256 | 1717600 | 2019 | 29 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A UHPLC-MS/MS method coupled with liquid-liquid extraction for the quantitation of phenacetin, omeprazole, metoprolol, midazolam and their metabolites in rat plasma and its application to the study of four CYP450 activities
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Drug-drug interactions (DDIs) are thought to be associated with the inhibition of cytochrome P450 activities. The cocktail method with analysis of the metabolism of two or more probe drugs is used to determine CYP450 activities. In this study, we established a UHPLC-MS/MS method for simultaneous quantitation of four CYP450 probe drugs (phenacetin, omeprazole, metoprolol and midazolam) and their metabolites (acetaminophen, 5â²-hydroxy omeprazole, α-hydroxy metoprolol and 1â²-hydroxy midazolam) in rat plasma. Sample preparation by plasma protein precipitation was combined with a liquid-liquid extraction method. The separation was carried out on a ZORBAX Eclipse Plus C18 Rapid Resolution High Definition column with a gradient elution, using water containing 0.1% formic acid (A) and acetonitrile (B) in a run time of only 3.0âmin. Detection was conducted with a 6420 series triple-quadrupole tandem mass spectrometer, using ESI in positive ion mode with multiple reaction monitoring (MRM). The calibration curves were linear over the concentration range 10-5000âng/mL for phenacetin, omeprazole, metoprolol and midazolam, and 1-500âng/mL for their metabolites. Intra- and inter-day precisions were within 15%, and the accuracies were in the range of 87-112%. The method was successfully applied to the pharmacokinetic study of probe drugs/metabolites and DDIs with 3-n-butylphthalide (NBP) after administration of a single oral dose of phenacetin, omeprazole, metoprolol and midazolam in rats.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 163, 30 January 2019, Pages 204-210
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 163, 30 January 2019, Pages 204-210
نویسندگان
Zhe Wang, Wei Sun, Zheng-Feng Lin, Rui Sun, Cheng-Ke Huang, Wei-Jian Ye, Yao-Yao Dong, Xiao-Dan Zhang, Rui-Jie Chen,